Roles of Mitochondrial DNA Damage in Kidney Diseases: A New Biomarker

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Dec 11

PMID 36499488

Authors

Jun Feng

Zhaowei Chen

Wei Liang

Zhongping Wei

Guohua Ding

Affiliations

Soon will be listed here.

Abstract

The kidney is a mitochondria-rich organ, and kidney diseases are recognized as mitochondria-related pathologies. Intact mitochondrial DNA (mtDNA) maintains normal mitochondrial function. Mitochondrial dysfunction caused by mtDNA damage, including impaired mtDNA replication, mtDNA mutation, mtDNA leakage, and mtDNA methylation, is involved in the progression of kidney diseases. Herein, we review the roles of mtDNA damage in different setting of kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD). In a variety of kidney diseases, mtDNA damage is closely associated with loss of kidney function. The level of mtDNA in peripheral serum and urine also reflects the status of kidney injury. Alleviating mtDNA damage can promote the recovery of mitochondrial function by exogenous drug treatment and thus reduce kidney injury. In short, we conclude that mtDNA damage may serve as a novel biomarker for assessing kidney injury in different causes of renal dysfunction, which provides a new theoretical basis for mtDNA-targeted intervention as a therapeutic option for kidney diseases.

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References

van der Slikke E, Star B, van Meurs M, Henning R, Moser J, Bouma H . Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI. Crit Care. 2021; 25(1):36. PMC: 7831178. DOI: 10.1186/s13054-020-03424-1. View

Zhang X, Wu X, Hu Q, Wu J, Wang G, Hong Z . Mitochondrial DNA in liver inflammation and oxidative stress. Life Sci. 2019; 236:116464. DOI: 10.1016/j.lfs.2019.05.020. View

Milenkovic D, Sanz-Moreno A, Calzada-Wack J, Rathkolb B, Amarie O, Gerlini R . Mice lacking the mitochondrial exonuclease MGME1 develop inflammatory kidney disease with glomerular dysfunction. PLoS Genet. 2022; 18(5):e1010190. PMC: 9119528. DOI: 10.1371/journal.pgen.1010190. View

Liu Z, Tian J, Peng F, Wang J . Hypermethylation of mitochondrial DNA facilitates bone metastasis of renal cell carcinoma. J Cancer. 2022; 13(1):304-312. PMC: 8692697. DOI: 10.7150/jca.62278. View

McMillan R, Stewart S, Budnick J, Caswell C, Hulver M, Mukherjee K . Quantitative Variation in m.3243A > G Mutation Produce Discrete Changes in Energy Metabolism. Sci Rep. 2019; 9(1):5752. PMC: 6453956. DOI: 10.1038/s41598-019-42262-2. View

Szeto C, Lai K, Chow K, Kwan B, Cheng P, Kwong V . Plasma Mitochondrial DNA Level is a Prognostic Marker in Peritoneal Dialysis Patients. Kidney Blood Press Res. 2016; 41(4):402-12. DOI: 10.1159/000443442. View

Feng Y, Imam Aliagan A, Tombo N, Draeger D, Bopassa J . RIP3 Translocation into Mitochondria Promotes Mitofilin Degradation to Increase Inflammation and Kidney Injury after Renal Ischemia-Reperfusion. Cells. 2022; 11(12). PMC: 9220894. DOI: 10.3390/cells11121894. View

Longchamps R, Yang S, Castellani C, Shi W, Lane J, Grove M . Genome-wide analysis of mitochondrial DNA copy number reveals loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation. Hum Genet. 2021; 141(1):127-146. PMC: 8758627. DOI: 10.1007/s00439-021-02394-w. View

Ji X, Guo W, Gu X, Guo S, Zhou K, Su L . Mutational profiling of mtDNA control region reveals tumor-specific evolutionary selection involved in mitochondrial dysfunction. EBioMedicine. 2022; 80:104058. PMC: 9121266. DOI: 10.1016/j.ebiom.2022.104058. View

10.

Cai M, Yu Q, Bao J . A case report of mitochondrial myopathy with membranous nephropathy. BMC Nephrol. 2022; 23(1):87. PMC: 8895630. DOI: 10.1186/s12882-022-02710-0. View

11.

Eirin A, Herrmann S, Saad A, Abumoawad A, Tang H, Lerman A . Urinary mitochondrial DNA copy number identifies renal mitochondrial injury in renovascular hypertensive patients undergoing renal revascularization: A Pilot Study. Acta Physiol (Oxf). 2019; 226(3):e13267. PMC: 6556125. DOI: 10.1111/apha.13267. View

12.

Liu Q, Krishnasamy Y, Rehman H, Lemasters J, Schnellmann R, Zhong Z . Disrupted Renal Mitochondrial Homeostasis after Liver Transplantation in Rats. PLoS One. 2015; 10(10):e0140906. PMC: 4610703. DOI: 10.1371/journal.pone.0140906. View

13.

Fukunaga H . Mitochondrial DNA Copy Number and Developmental Origins of Health and Disease (DOHaD). Int J Mol Sci. 2021; 22(12). PMC: 8235559. DOI: 10.3390/ijms22126634. View

14.

Connor T, Hoer S, Mallett A, Gale D, Gomez-Duran A, Posse V . Mutations in mitochondrial DNA causing tubulointerstitial kidney disease. PLoS Genet. 2017; 13(3):e1006620. PMC: 5360345. DOI: 10.1371/journal.pgen.1006620. View

15.

Imasawa T, Tanaka M, Yamaguchi Y, Nakazato T, Kitamura H, Nishimura M . 7501 T > A mitochondrial DNA variant in a patient with glomerulosclerosis. Ren Fail. 2014; 36(9):1461-5. DOI: 10.3109/0886022X.2014.945181. View

16.

Ding M, Tolbert E, Birkenbach M, Gohh R, Akhlaghi F, Ghonem N . Treprostinil reduces mitochondrial injury during rat renal ischemia-reperfusion injury. Biomed Pharmacother. 2021; 141:111912. PMC: 8429269. DOI: 10.1016/j.biopha.2021.111912. View

17.

Ding P, Tan Q, Wei Z, Chen Q, Wang C, Qi L . Toll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation. Bone Res. 2022; 10(1):42. PMC: 9142495. DOI: 10.1038/s41413-022-00210-3. View

18.

Huang Y, Zhou J, Zhang H, Canfran-Duque A, Singh A, Perry R . Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance. J Clin Invest. 2022; 132(9). PMC: 9057632. DOI: 10.1172/JCI148852. View

19.

McArthur K, Whitehead L, Heddleston J, Li L, Padman B, Oorschot V . BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science. 2018; 359(6378). DOI: 10.1126/science.aao6047. View

20.

Zhang J, Shang J, Wang F, Huo X, Sun R, Ren Z . Decreased mitochondrial D-loop region methylation mediates an increase in mitochondrial DNA copy number in CADASIL. Clin Epigenetics. 2022; 14(1):2. PMC: 8725280. DOI: 10.1186/s13148-021-01225-z. View